Publication

Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice

Müller, C., Zidek, L. M., Ackermann, T., de Jong, T., Liu, P., Kliche, V., Zaini, M. A., Kortman, G., Harkema, L., Verbeek, D. S., Tuckermann, J. P., von Maltzahn, J., de Bruin, A., Guryev, V., Wang, Z-Q. & Calkhoven, C. F., 4-Jun-2018, In : eLife. 7, 28 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Müller, C., Zidek, L. M., Ackermann, T., de Jong, T., Liu, P., Kliche, V., ... Calkhoven, C. F. (2018). Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice. eLife, 7. https://doi.org/10.7554/eLife.34985

Author

Müller, Christine ; Zidek, Laura M ; Ackermann, Tobias ; de Jong, Tristan ; Liu, Peng ; Kliche, Verena ; Zaini, Mohamad Amr ; Kortman, Gertrud ; Harkema, Liesbeth ; Verbeek, Dineke S ; Tuckermann, Jan P ; von Maltzahn, Julia ; de Bruin, Alain ; Guryev, Victor ; Wang, Zhao-Qi ; Calkhoven, Cornelis F. / Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice. In: eLife. 2018 ; Vol. 7.

Harvard

Müller, C, Zidek, LM, Ackermann, T, de Jong, T, Liu, P, Kliche, V, Zaini, MA, Kortman, G, Harkema, L, Verbeek, DS, Tuckermann, JP, von Maltzahn, J, de Bruin, A, Guryev, V, Wang, Z-Q & Calkhoven, CF 2018, 'Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice', eLife, vol. 7. https://doi.org/10.7554/eLife.34985

Standard

Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice. / Müller, Christine; Zidek, Laura M; Ackermann, Tobias; de Jong, Tristan; Liu, Peng; Kliche, Verena; Zaini, Mohamad Amr; Kortman, Gertrud; Harkema, Liesbeth; Verbeek, Dineke S; Tuckermann, Jan P; von Maltzahn, Julia; de Bruin, Alain; Guryev, Victor; Wang, Zhao-Qi; Calkhoven, Cornelis F.

In: eLife, Vol. 7, 04.06.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Müller C, Zidek LM, Ackermann T, de Jong T, Liu P, Kliche V et al. Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice. eLife. 2018 Jun 4;7. https://doi.org/10.7554/eLife.34985


BibTeX

@article{b89108dbcd1f46f3871a57da42d7daed,
title = "Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice",
abstract = "Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb-mRNA. Here we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBPβΔuORF mice display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBPβ in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBPβ-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.",
keywords = "TRANSCRIPTION FACTOR, CALORIC RESTRICTION, BINDING-PROTEIN-ALPHA, DIETARY RESTRICTION, GENETICALLY HETEROGENEOUS MICE, IMPROVES METABOLIC HEALTH, MESSENGER-RNA TRANSLATION, ESTROGEN-RECEPTOR-ALPHA, EIF2-ALPHA KINASE GCN2, GENE-EXPRESSION",
author = "Christine M{\"u}ller and Zidek, {Laura M} and Tobias Ackermann and {de Jong}, Tristan and Peng Liu and Verena Kliche and Zaini, {Mohamad Amr} and Gertrud Kortman and Liesbeth Harkema and Verbeek, {Dineke S} and Tuckermann, {Jan P} and {von Maltzahn}, Julia and {de Bruin}, Alain and Victor Guryev and Zhao-Qi Wang and Calkhoven, {Cornelis F}",
note = "{\circledC} 2018, M{\"u}ller et al.",
year = "2018",
month = "6",
day = "4",
doi = "10.7554/eLife.34985",
language = "English",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "ELIFE SCIENCES PUBLICATIONS LTD",

}

RIS

TY - JOUR

T1 - Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice

AU - Müller, Christine

AU - Zidek, Laura M

AU - Ackermann, Tobias

AU - de Jong, Tristan

AU - Liu, Peng

AU - Kliche, Verena

AU - Zaini, Mohamad Amr

AU - Kortman, Gertrud

AU - Harkema, Liesbeth

AU - Verbeek, Dineke S

AU - Tuckermann, Jan P

AU - von Maltzahn, Julia

AU - de Bruin, Alain

AU - Guryev, Victor

AU - Wang, Zhao-Qi

AU - Calkhoven, Cornelis F

N1 - © 2018, Müller et al.

PY - 2018/6/4

Y1 - 2018/6/4

N2 - Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb-mRNA. Here we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBPβΔuORF mice display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBPβ in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBPβ-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.

AB - Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb-mRNA. Here we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBPβΔuORF mice display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBPβ in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBPβ-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.

KW - TRANSCRIPTION FACTOR

KW - CALORIC RESTRICTION

KW - BINDING-PROTEIN-ALPHA

KW - DIETARY RESTRICTION

KW - GENETICALLY HETEROGENEOUS MICE

KW - IMPROVES METABOLIC HEALTH

KW - MESSENGER-RNA TRANSLATION

KW - ESTROGEN-RECEPTOR-ALPHA

KW - EIF2-ALPHA KINASE GCN2

KW - GENE-EXPRESSION

U2 - 10.7554/eLife.34985

DO - 10.7554/eLife.34985

M3 - Article

VL - 7

JO - eLife

JF - eLife

SN - 2050-084X

ER -

ID: 61355590